Is DLAT p.Ala175Pro (c.523G>C) pathogenic?

DLAT p.Ala175Pro (c.523G>C) is classified Uncertain significance in DLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: ambiguous (0.3912); Very rare (popmax 0.00381%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DLAT p.Ala175Pro (c.523G>C)?

DLAT p.Ala175Pro (c.523G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DLAT p.Ala175Pro (c.523G>C) in the general population?

DLAT p.Ala175Pro (c.523G>C) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about DLAT p.Ala175Pro (c.523G>C)?

AlphaMissense predicts ambiguous (score 0.3912) — an in-silico prediction, not a clinical call.

DLAT p.Ala175Pro

c.523G>C · VCV3272196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3912	ambiguous
REVEL	0.317	indeterminate
SaProt	LLR -11.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 0.89, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.014 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00381% European (non-Finnish) · 45/1,180,002 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00308% 45/1,461,870 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLAT
Protein: p.Ala175Pro
Coding: c.523G>C
MANE Select: NM_001931
Type: single nucleotide variant
Location: chr11:112028808 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 13 PDB
Residue 175: an α-helix

Full DLAT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLAT p.Ala175Gly Uncertain significance ★ ⚠ same residue
DLAT p.Val157Gly Likely pathogenic ★★ same condition
DLAT p.Ala253Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg429Ser Uncertain significance ★★ ⚠ same condition
DLAT p.Arg430Gln Uncertain significance ★★ ⚠ same condition
DLAT p.Arg56Pro Uncertain significance ★★ ⚠ same condition
DLAT p.Arg70Trp Uncertain significance ★★ ⚠ same condition
DLAT p.Asp390Asn Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dlat-p-ala175pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown